Sinopodophyllum hexandrum is a perennial anti-cancer medicinal plant as unique phytochemical composition podophyllotoxin, and it has special effects on the treatments of pneumonic, cervical and testicular cancers. Besides the podophyllotoxin, phenolic substances play a key role in the clinical practice. However, few reports were available in terms of the phenolic compositions and antioxidant activity. In this work, main phenolic compounds were quantified by RP-HPLC in seven organs from S. hexandrum. Simultaneously, the sodium borohydride/chloranil-based (SBC) method and the Folin-Ciocalteau colorimetric method were used to determine total flavonoids and total phenols contents, respectively. The antioxidant activity of the different organs was further assessed by three methods (DPPH method, ABTS method and FRAP method). Phenolic compositions/total flavonoids contents/total phenols contents/antioxidant activity was observed to have significant differences among different organs (P<0.05), but have a consistent changing rule viz. rhizome>root>fruit>flower>leaf>stem>petiole. Furthermore, a correlation analysis was employed and indicated that a positive correlation existed between phenolic compositions contents and antioxidant activity. Obviously, rhizome had high phenolic compositions contents and strong antioxidant activity with the low DPPHIC50 value of 23.52 μg/mL, high ABTS value of 1137.82 μmol equiv. Trolox/g and high FRAP value of 685.76 μmol equiv. Trolox/g. Therefore, rhizome is recommended as a preponderant medicinal part, and root is proposed as an alternative raw material resource for natural antioxidant agents in functional food, medicine and chemicals. This study can provide a new insight into the utilization extension of S. hexandrum resources.